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Biomedical subjects

A Patat

Publications and source records attributed to A Patat.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers.

1. The possible interaction between a new H1 antihistamine, mizolastine, and lorazepam was assessed in a randomised, double-blind, cross-over, placebo-controlled study involving 16 healthy young male volunteers who received mizolastine 10 mg or placebo once daily for 8 days with a 1 week wash-out interval. The interaction of mizolastine, at steady-state, with a single oral dose of lorazepam or placebo was assessed on days 6 or 8 of each treatment period. 2. Psychomotor performance and cognitive function were evaluated using objective tests (critical flicker fusion threshold, choice reaction time, tapping, arithmetic calculation, body sway) and self-ratings (visual analogue scale, ARCI) before and at 2, 4, 6 and 8 h after dosing. Short-term memory (Sternberg memory scanning immediate free recall of a word list) and long-term memory (delayed free recall and recognition of words and pictures) were assessed before and at 3 h after dosing. Pharmacodynamic interactions were evaluated by repeated measures ANOVA in a 2 x 2 factorial interaction model. 3. Mizolastine, 10 mg once daily, at steady-state, was devoid of sedation and detrimental effect on skilled performance and memory. 4. In contrast, a single 2 mg dose of lorazepam produced marked impairment of psychomotor performance, cognitive functions (significant reduction in flicker fusion threshold, tapping and arithmetic calculation and increase in reaction times and body sway) and subjective sedation from 2 to 8 h after dosing. In addition, lorazepam induced an anterograde amnesia, characterised by a decrease in delayed free recall and recognition, and a deficit in short term memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The psychomotor and cognitive effects of litoxetine in young and middle aged volunteers.

1. The effects of a range of doses of litoxetine (twice daily for 4 days), a novel specific serotonin re-uptake inhibitor, were evaluated in young and middle aged volunteers. 2. Psychometric testing was carried out at various time points on days 1 and 4 of each treatment period. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT), Stroop and Sternberg memory scanning tests. Subjective feelings of sleep and sedation were measured by the Leeds Sleep Evaluation Questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic profiles were determined from analyses of blood samples taken after the final dose on day 5. 4. Overall, there were few changes in any of the psychometric tests and although the higher doses of litoxetine improved CFF, these effects were weak in that differences could only be detected when the results were pooled against time. 5. The pharmacokinetic profile of litoxetine was very similar in both the young and middle aged subjects, and there was no difference regarding tolerability. 6. There is little evidence from this study to suggest that litoxetine has any intrinsic sedative activity which is likely to interfere with the performance of activities of everyday life.

Administration, Oral↗
PubMed1994

EEG profile of intravenous zolpidem in healthy volunteers.

Zolpidem is an imidazopyridine which binds specifically to the omega 1 receptor. Zolpidem demonstrated potent hypnotic activity at a dose of 10 mg. Pharmacodynamics and pharmacokinetics of zolpidem were studied after daytime administration in a randomised, double-blind, placebo-controlled, cross-over trial. Single doses of zolpidem (10 mg IV as a 3-min infusion and 20 mg orally) and placebo were firstly tested in 12 healthy young male volunteers. Two other doses (5 mg IV and orally) were then evaluated in 6 out of these 12 subjects. EEG (4 leads = Fp2-T4, Fp1-T3, T4-02 and T3-01), and Stanford Sleepiness Scale (SSS) were measured up to 5 h postdosing. Blood samples were also collected up to 24 h. The time course of the hypnotic activity of zolpidem, assessed by the score obtained on SSS, showed a similar profile whatever the route or the dose administered: slightly earlier onset after IV but sedative scores were reached at 30 min and the effect peaked between 1 and 1.5 h and lasted 4 h in both conditions. The EEG profile of zolpidem was characterised by a decrease of alpha activity and an increase in delta and in beta activity. The effect on beta activity was marked within the first hour and then disappeared. The time course of delta and alpha activities indicated a rapid onset (10 min after IV, 30 min after oral route) and a duration of 3-4 h. The amplitude of these relative EEG changes and their duration were independent of the route of administration and the dose administered. AUC and Cmax increased proportionally to the administered dose and elimination half life (2h), clearance and volume of distribution did not change according to the dose or the route of administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Flumazenil antagonizes the central effects of zolpidem, an imidazopyridine hypnotic.

Zolpidem is a new imidazopyridine-hypnotic that selectively binds to the central omega 1-receptor subtype. A double-blind, randomized, three-way, crossover placebo-controlled study was carried out in nine healthy male volunteers to assess the possible antagonism of central nervous system--depressant effects of zolpidem by flumazenil. Subjects received zolpidem (0.21 mg/kg) or placebo, intravenously, followed 17 minutes later by flumazenil (0.04 mg/kg) or placebo. Vigilance and performance were assessed by a trained anesthetist with use of ciliary reflex, response to a verbal instruction, subjective sedation, a tracking task, and a free recall task. Zolpidem produced a clinically relevant hypnotic effect in five subjects and significantly impaired performance in all nine subjects up to 90 minutes after dosing. Flumazenil rapidly antagonized clinical sedation in the five subjects who were asleep and significantly reversed the performance decrement within 3 minutes, without any escape phenomenon. Flumazenil did not change zolpidem plasma concentrations, confirming the pharmacodynamic nature of the interaction. Flumazenil may thus be a safe and effective antidote in patients with zolpidem overdosage.

Adult↗
PubMed1994

Effects of mizolastine, a new antihistamine, on psychomotor performance and memory in elderly subjects.

The effects of a single 10 mg dose of the new H1 antihistamine mizolastine on psychomotor performance and memory in the elderly were assessed in a double-blind, cross-over, placebo-controlled study in 15 elderly female volunteers aged 66-77 years, using clemastine 2 mg as a positive control. Objective (critical flicker fusion, choice reaction time, digit symbol substitution, immediate and delayed free recall) and subjective (linear analogue rating scales) assessments were done on each test day before the dose, then 4 and 8 h post-dose. Plasma samples were also collected. A single oral dose of mizolastine within the range of recommended daily therapeutic dosages (10 mg) failed to induce subjective drowsiness and produced no detrimental effects on psychomotor performance or on short-term and long-term memory in the elderly subjects. In contrast, 2 mg clemastine induced significant impairments (decrease in critical flicker fusion, increase in recognition reaction time) in comparison with placebo and mizolastine, although it did not impair memory. The pharmacokinetic profile of mizolastine in the elderly study subjects was similar to that observed in healthy young volunteers. Therefore, it can be concluded that mizolastine 10 mg could be used safely in elderly out-patients as it preserves functions involved in activities of daily living.

Aged↗
PubMed1994

Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist.

The possible effects on memory, psychomotor performance and mood of eliprodil, a new non-competitive NMDA receptor antagonist acting through the polyamine modulatory site, was assessed in a randomized, double-blind, cross-over, placebo-controlled study involving 11 healthy young male volunteers. Eliprodil 30 mg, a placebo and midazolam 15 mg, a positive control, were administered as a single oral dose at 1 week wash-out intervals. Objective tests evaluated both memory (Sternberg memory scanning and paired words for short-term memory, delayed free recall of pictures for long-term memory) and psychomotor functions and arousal (critical flicker fusion threshold, choice reaction time, body sway). Mood was assessed using self-ratings (LARS, POMS, ARCI). Statistical analysis was performed using an ANOVA with pairwise comparisons using Tukey's method. A single dose of eliprodil 30 mg was free of any detrimental effect on memory and skilled performance and did not produce either subjective sedation or excitation or psychotomimetic effects in comparison with placebo. In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory). The potent sedative activity of midazolam, peaking 1 to 3 h post-dose, was confirmed by subjective evaluation and had disappeared 8 h post-dose.

Adult↗
PubMed1994

EEG profile of litoxetine after single and repeated administration in healthy volunteers.

1. Litoxetine is a selective serotonin reuptake inhibitor with antidepressant activity in animal models and in depressed patients. 2. This double-blind, cross-over, placebo-controlled study was carried out in 12 healthy young male volunteers. The aim was to assess the EEG profile of litoxetine in parallel with its pharmacokinetics after a single dose or multiple administrations for 4 days (6 doses) of two dosages (10 mg and 25 mg). Spectral analysis of four EEG leads (F4-T4, F3-T3, T4-02 and T3-01) was done up to 12 h post-dose. 3. In single or multiple doses, litoxetine induced EEG changes characterised by a dose-related increase in fast beta energies, mainly beta 2, without any changes in slow waves (delta and theta). A slight reduction in alpha activity occurred only after repeated doses. 4. EEG changes occurred after a single oral administration and lasted at least 12 h with litoxetine blood concentrations ranging from 4 to 10 ng ml-1. With repeated administrations, the pharmacodynamic steady-state was achieved as the increase in beta 2 energies was the same before and 12 h post-dose. These effects occurred with litoxetine blood concentrations ranging from 3 to 7 ng ml-1 with the 10 mg dosage and from 8 to 18 ng ml-1 with the 25 mg dosage. The EEG profile did not change after 4 days of repeated administration, indicating that tolerance did not develop. 5. Cmax and AUC showed proportionality between the administered dosages of 10 and 25 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Assessment of the anticholinergic effect of the new antihistamine mizolastine in healthy subjects.

1. Twelve healthy subjects were enrolled in a double-blind placebo controlled cross-over study in order to assess the possible anticholinergic effects of four doses of a new antihistamine compound, mizolastine, compared with hyoscine butylbromide (HBB) used as a reference anticholinergic drug. 2. Although mizolastine, a potent and selective H1-receptor blocker has no affinity for muscarinic receptors and does not antagonize the effects of carbachol in rodents, a study was initiated to investigate its effects on various effectors possessing muscarinic receptors (eye, heart, sweat gland, salivary gland). 3. HBB (40 mg, s.c.) impaired accommodation, decreased salivary flow and inhibited cardiac sinus arrhythmia. Pupil diameter and maximum constriction speed, carbachol-induced skin sweating and Valsalva ratio were unaffected. 4. Mizolastine (5, 10, 20, 40 mg p.o.) did not affect any parameter at any time point, demonstrating a lack of anticholinergic effect.

Adult↗
PubMed1991

RU 41,656 does not reverse the scopolamine-induced cognitive deficit in healthy volunteers.

The potential antagonism of a single oral dose of RU 41,656 10 mg on the memory and attention disturbances induced by scopolamine 0.6 mg s.c. have been investigated in a 3 period, placebo controlled, double blind, cross over study in 12 healthy, young volunteers. The effects of the compounds were evaluated by objective tests (Buschke selective reminding test, CFF, simple reaction time, tapping, arithmetical calculation) and subjective measurements (visual analogue scale, side effects questionnaire). Measurements were taken before treatment and 2, 4 and 7 h after RU 41,656. Scopolamine caused anterograde amnesia and sedative effects as which were not counteracted by RU 41,656.

Adult↗
PubMed1991

Study of the potential reversal of triazolam memory and cognitive deficits by RU 41 656 in healthy subjects.

The potential antagonism of a single oral dose of RU 41 656 (10 mg) on the memory and attention disturbances induced by oral administration of triazolam (0.25 mg) have been investigated in a 3-period, placebo controlled, double blind, cross-over study involving 12 healthy young volunteers. The effects of the compounds were evaluated by objective tests (Buschke selective reminding test, CFF, simple reaction time, tapping, arithmetical calculation) and subjective measurements (visual analogue scale, side effects questionnaire). Measurements were taken before treatment and 2, 4 and 7 h after RU 41 656 intake. Triazolam caused anterograde amnesia as already described with other benzodiazepine with few sedative effects at this dosage. Under the experimental conditions of the trial, RU 41 656 failed to counteract the memory deficits induced by triazolam.

Adult↗
PubMed1989

Safety and tolerance of single oral doses of trandolapril (RU 44.570), a new angiotensin converting enzyme inhibitor.

The safety and tolerance of single oral doses of a new angiotensin converting enzyme (ACE) inhibitor, trandolapril have been examined in 90 healthy male volunteers, in a randomised, double blind, placebo-controlled study. The subjects were divided into 10 groups, each of 9 subjects and treatments (6 subjects on trandolapril and 3 on placebo per group) were allocated by unbalanced randomisation. Ten single, increasing oral doses were tested: 0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 24 and 32 mg. The assessment criteria were clinical (monitoring of blood pressure, heart and respiratory rate, electrocardiogram, temperature and evaluation of behaviour and side effects) and routine laboratory tests. Blood pressure did not fall except for a slight drop in diastolic pressure during the first 4 h following the 32-mg dose. However, although an effect of the compound cannot be excluded, the reduction in blood pressure may have reflected intersubject variability. No orthostatic hypotension was observed. There was no change in the other vital signs, and in particular no increase in heart rate was observed. No serious adverse effect was encountered. The pharmacological activity of the compound was studied by assaying plasma ACE activity. Inhibition of ACE was linearly dose-dependant from 0 (placebo) to 2 mg, and above that dose, the inhibition was nearly total. ACE activity was markedly reduced within 30 min after administration of trandolapril, and maximal inhibition was observed from 2-4 h onwards, lasting for up to 24 h after dosing. For doses above 2 mg, inhibition was still 40% of the basal activity on Day 8 after dosing.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Acute effects of amitriptyline on human performance and interactions with diazepam.

The effects of psychomotor performance and attention of amitriptyline 75 mg administered without and with diazepam 10 mg have been investigated in 12 healthy subjects. The effects of the compounds were evaluated by objective tests (measurement of body sway, critical flicker fusion, visual reaction time, tachistoscopy, short term visual memory, tapping test, arithmetical calculation and Clement's code) and subjective measurements (visual analogue scales and side effects questionnaire). Measurements were taken before treatment and after 1, 3, 6, 8 and 24 h. Placebo did not affect either the objective or the subjective measurements. Diazepam caused a reduction in attention and performance after 1 h which had disappeared at 3 h. Amitriptyline caused a marked reduction in attention and performance, reaching a peak 3 hours after drug administration and persisting until 8 h. the deterioration in vigilance induced by amitriptyline was potentiated by concomitant diazepam.

Adult↗
PubMed1988

Acute effects on psychomotor performance of binedaline alone and with alcohol.

The effects of single oral doses of binedaline (100 mg), imipramine (50 mg) and placebo administered without and with alcohol (0.8 g/kg) were compared on performance tasks (posturographic recordings, i.e., body sway to study alertness, squares test to explore attention and concentration) and subjective assessments in 12 healthy volunteers. The tasks were completed 1.4 and 8 h after drug administration. Blood samples were collected at the same times. Binedaline had no significant effects on any of the task parameters and did not interact with alcohol. Imipramine alone impaired performance at 4 h as shown on posturographic parameters. These disturbances were potentiated by the intake of alcohol. No pharmacokinetic interaction was noted.

Adult↗
PubMed1987

Effects of single oral doses of clobazam, diazepam and lorazepam on performance tasks and memory.

The effects on memory and psychomotor performance and the subjective effects of three anxiolytic benzodiazepines (lorazepam 2 mg, diazepam 10 mg and clobazam 20 mg p.o.) have been evaluated in a double-blind, placebo-controlled, cross-over study in 10 healthy volunteers. At each session, measurements were made prior to and +3.5 h after drug administration, except in the case of REY's test, which was presented at H + 1 h (learning) and was evaluated at H + 8 h and at H + 24 h (delayed recall). Single clinical doses of diazepam and lorazepam caused anterograde amnesia by disturbing acquisition, consolidation and retrieval. Clobazam did not impair memory. Lorazepam impaired performances in all the tests used to evaluate perception, immediate memory, reaction time, psychomotor skill and intellectual capacity. Diazepam caused a decrease in cortical arousal and the speed of perception of visual stimuli, whereas clobazam increased reaction time and reduced cortical arousal. Lorazepam caused a significant degradation of performance relative to the other two treatments.

Adult↗
PubMed1985

Dose-response relationship of vindeburnol based on spectral analysis of posturographic recordings.

The dose-response relationship of vindeburnol has been investigated by assessing postural activity in a population of elderly patients, using posturography, an objective method for measuring balance. A controlled double blind trial was done in two periods: during the first week each patient received placebo, and during the second week either placebo or vindeburnol 30, 60 or 90 mg/d was given. Subjects underwent three posturographic recordings at weekly intervals (prior to treatment, after one week on placebo and after one week of treatment). There was no placebo effect. A significant decrease in the sagittal and lateral energies of body sway was found after vindeburnol, which indicates an improvement in balance. The improvement was proportional to the daily dose of vindeburnol.

Aged↗
PubMed1985

Effect on postural sway of various benzodiazepine tranquillizers.

The effects of various benzodiazepine tranquillizers (clobazam 20 mg, bromazepam 6 mg and lorazepam 2 mg) were investigated by posturography in 16 subjects in a controlled trial. Twelve received each of the three anxiolytics for 1 week in a cross-over design, four received placebo for 1 week during the three successive treatment periods. A pharmacodynamic study was carried out after the first administration, and another assessment was done after 1 week of treatment. The first administration of lorazepam caused the most marked disturbances of body sway (increase of spectral energies, length and amplitude of the stabilogram). The first administration of bromazepam was also accompanied by an increase of the posturographic parameters, although less marked. Administration of clobazam did not produce any impairment of equilibrium, indicating that it is devoid of any sedative effect measurable by posturography. No changes of the postural sway can be detected on the measurement recorded 10 h after the last dose of 1 week's treatment.

Adult↗